Stressful life events and genetic liability to major depression: genetic control of exposure to the environment?

BACKGROUND: Although overwhelming evidence suggests that genetic and environmental risk factors both contribute to the aetiology of major depression (MD), we know little of how these two risk factor domains inter-relate. In particular, can the genetic liability to MD increase the risk of experiencing stressful life events (SLEs)? METHODS: Using discrete time survival analysis in a population-based sample of 2164 female twins, we examined whether the risks for nine personal and three aggregate network SLEs were predicted by the level of genetic liability to MD, indexed by the lifetime history of MD in monozygotic and dizygotic co-twins. RESULTS: Genetic liability to MD was associated with a significantly increased risk for six personal SLEs (assault, serious marital problems, divorce/breakup, job loss, serious illness and major financial problems) and one network SLE (trouble getting along with relatives/friends). This effect was not due to SLEs occurring during depressive episodes. Similar results were found using structural equation twin modelling. In contrast to the pattern observed with MD, the genetic liability to alcoholism impacted on the risk for being robbed and having trouble with the law. CONCLUSION: In women, genetic risk factors for MD increase the probability of experiencing SLEs in the interpersonal and occupational/financial domains. Genes can probably impact on the risk for psychiatric illness by causing individuals to select themselves into high risk environments.

Resemblance of psychotic symptoms and syndromes in affected sibling pairs from the Irish Study of High-Density Schizophrenia Families: evidence for possible etiologic heterogeneity.

OBJECTIVE: The authors sought to determine whether the clinical manifestations of schizophrenia and other psychotic disorders are correlated in affected sibling pairs. METHOD: They examined, in 256 sibling pairs concordant for DSM-III-R schizophrenia and 457 sibling pairs concordant for all nonaffective psychoses ascertained in the Irish Study of High-Density Schizophrenia Families, similarity for 1) symptoms, course, and outcome; 2) symptom factors; and 3) syndromes, defined by latent class analysis. RESULTS: Global course and outcome, as well as all major symptoms except hallucinations, were modestly but significantly correlated in sibling pairs concordant for schizophrenia. Three symptom factors-negative symptoms, positive symptoms, and affective symptoms-were all significantly correlated in concordant sib pairs. Latent class analysis suggested five schizophrenic syndromes. Class membership was significantly correlated in concordant sibling pairs. Similar results were found for sibling pairs concordant for nonaffective psychoses. CONCLUSIONS: The clinical manifestations of the schizophrenic syndrome (both narrowly and broadly defined) are moderately influenced by familial factors. From a familial/genetic perspective, schizophrenia as currently defined may be etiologically heterogeneous.

Age at onset in schizophrenia and risk of illness in relatives. Results from the Roscommon Family Study.

BACKGROUND: For many common medical and neuropsychiatric disorders, early age at onset reflects high familial liability to illness. However, for schizophrenia, most studies do not find such a relationship. METHOD: Using Cox proportional hazard modes, we investigate this question in the epidemiologically-based Roscommon family study. RESULTS: No relationship was found between age at onset in schizophrenic probands and the hazard rate for schizophrenia in their relatives. Similar results were obtained when the definition of illness was expanded to include schizoaffective disorder and other non-affective psychoses. CONCLUSIONS: For schizophrenia, a 'common-sense' model for age of onset (i.e. those with highest familial liability to illness succumb first while those with lower liability survive longer before falling ill) does not seem to apply. Our results are more consistent with a model in which variation in age at onset of schizophrenia is due to random developmental effects or to environmental experiences unique to the individual.

The risk for psychiatric illness in siblings of schizophrenics: the impact of psychotic and non-psychotic affective illness and alcoholism in parents.

Clarification of the nature of the liability to schizophrenia transmitted within families is a major goal of family studies. In the Roscommon Family Study, the risk in relatives of schizophrenic vs. control probands was significantly increased for psychotic affective illness (PAI), but not for non-psychotic affective illness (NPAI) or alcoholism (ALC). We attempt to confirm these findings independently by examining, within families of schizophrenia spectrum probands, the relationship between PAI, NPAI and ALC in parents and the risk for schizophrenia spectrum disorders in siblings. A parental diagnosis of PAI predicted a significantly increased risk for schizophrenia, affective illness and anxiety disorders in siblings. In particular, schizophrenia in siblings was predicted by a parental diagnosis of mood-incongruent PAI. By contrast, neither a parental diagnosis of NPAI nor a parental diagnosis of ALC was associated with an increased risk for schizophrenia spectrum disorders in siblings. Consistent with our earlier findings, these results suggest that (a) the familial liability to schizophrenia is neither extremely non-specific nor extremely specific and (b) PAI, and particularly mood-incongruent PAI, may occur particularly in parents of schizophrenics because, although it reflects a significant familial liability to schizophrenia, it does not markedly impair the ability to marry and reproduce.